NZ741130A - Tetrahydro-1h-pyrido[3,4-b]indole anti-estrogenic drugs - Google Patents
Tetrahydro-1h-pyrido[3,4-b]indole anti-estrogenic drugsInfo
- Publication number
- NZ741130A NZ741130A NZ741130A NZ74113016A NZ741130A NZ 741130 A NZ741130 A NZ 741130A NZ 741130 A NZ741130 A NZ 741130A NZ 74113016 A NZ74113016 A NZ 74113016A NZ 741130 A NZ741130 A NZ 741130A
- Authority
- NZ
- New Zealand
- Prior art keywords
- compound
- cancer
- pharmaceutically acceptable
- unsubstituted
- acceptable salt
- Prior art date
Links
Classifications
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/4353—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems
- A61K31/437—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom ortho- or peri-condensed with heterocyclic ring systems the heterocyclic ring system containing a five-membered ring having nitrogen as a ring hetero atom, e.g. indolizine, beta-carboline
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/44—Non condensed pyridines; Hydrogenated derivatives thereof
- A61K31/445—Non condensed piperidines, e.g. piperocaine
- A61K31/4523—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems
- A61K31/4545—Non condensed piperidines, e.g. piperocaine containing further heterocyclic ring systems containing a six-membered ring with nitrogen as a ring hetero atom, e.g. pipamperone, anabasine
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/435—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with one nitrogen as the only ring hetero atom
- A61K31/47—Quinolines; Isoquinolines
- A61K31/475—Quinolines; Isoquinolines having an indole ring, e.g. yohimbine, reserpine, strychnine, vinblastine
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K31/00—Medicinal preparations containing organic active ingredients
- A61K31/33—Heterocyclic compounds
- A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
- A61K31/495—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having six-membered rings with two or more nitrogen atoms as the only ring heteroatoms, e.g. piperazine or tetrazines
- A61K31/505—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim
- A61K31/506—Pyrimidines; Hydrogenated pyrimidines, e.g. trimethoprim not condensed and containing further heterocyclic rings
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K45/00—Medicinal preparations containing active ingredients not provided for in groups A61K31/00 - A61K41/00
- A61K45/06—Mixtures of active ingredients without chemical characterisation, e.g. antiphlogistics and cardiaca
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P15/00—Drugs for genital or sexual disorders; Contraceptives
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P19/00—Drugs for skeletal disorders
- A61P19/08—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease
- A61P19/10—Drugs for skeletal disorders for bone diseases, e.g. rachitism, Paget's disease for osteoporosis
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P33/00—Antiparasitic agents
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P35/00—Antineoplastic agents
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- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
- A61P5/00—Drugs for disorders of the endocrine system
- A61P5/24—Drugs for disorders of the endocrine system of the sex hormones
- A61P5/32—Antioestrogens
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- C—CHEMISTRY; METALLURGY
- C07—ORGANIC CHEMISTRY
- C07D—HETEROCYCLIC COMPOUNDS
- C07D471/00—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00
- C07D471/02—Heterocyclic compounds containing nitrogen atoms as the only ring hetero atoms in the condensed system, at least one ring being a six-membered ring with one nitrogen atom, not provided for by groups C07D451/00 - C07D463/00 in which the condensed system contains two hetero rings
- C07D471/04—Ortho-condensed systems
-
- A—HUMAN NECESSITIES
- A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
- A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
- A61K2300/00—Mixtures or combinations of active ingredients, wherein at least one active ingredient is fully defined in groups A61K31/00 - A61K41/00
Landscapes
- Health & Medical Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Organic Chemistry (AREA)
- Veterinary Medicine (AREA)
- Life Sciences & Earth Sciences (AREA)
- Animal Behavior & Ethology (AREA)
- General Health & Medical Sciences (AREA)
- Public Health (AREA)
- Medicinal Chemistry (AREA)
- Pharmacology & Pharmacy (AREA)
- Epidemiology (AREA)
- Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
- Chemical Kinetics & Catalysis (AREA)
- General Chemical & Material Sciences (AREA)
- Engineering & Computer Science (AREA)
- Bioinformatics & Cheminformatics (AREA)
- Physical Education & Sports Medicine (AREA)
- Endocrinology (AREA)
- Rheumatology (AREA)
- Orthopedic Medicine & Surgery (AREA)
- Reproductive Health (AREA)
- Tropical Medicine & Parasitology (AREA)
- Diabetes (AREA)
- Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
- Nitrogen Condensed Heterocyclic Rings (AREA)
- Medicines That Contain Protein Lipid Enzymes And Other Medicines (AREA)
- Low-Molecular Organic Synthesis Reactions Using Catalysts (AREA)
Abstract
The present disclosure provides tetrahydro-1H-pyrido[3,4-b]indole compounds or a pharmaceutically acceptable salt, optionally in a pharmaceutical composition, for the modulation of disorders mediated by estrogen, such as breast cancer, ovarian cancer, endometrial cancer, vaginal cancer, or other disorders as more fully described herein.
Claims (22)
1. A compound of Formula I: N R2 R8 R7 or a pharmaceutically acceptable salt thereof, wherein: X is -O-; R5 R5 N R5 N N Y is , or ; R1 and R2 are each en; R3 and R4 are each ndently selected from hydrogen and halo, and when one of R3 or R4 is halo, the other of R3 or R4 is hydrogen; R5 is unsubstituted C1-C6 alkyl; R6 is hydrogen, unsubstituted C1-C6 alkyl, C1-C6 haloalkyl, or unsubstituted C0-C4(C3-C6 cycloalkyl); and R7 and R8 are each independently selected from hydrogen and unsubstituted C1-C6 alkyl.
2. The compound of claim 1, wherein Y is .
3. The compound of claim 1 or claim 2, wherein Y is .
4. The compound of any one of claims 1 to 3, wherein R6 is C1-C6 haloalkyl.
5. The compound of any one of claims 1 to 4, wherein R7 is unsubstituted C1-C6 alkyl and R8 is hydrogen.
6. The compound of any one of claims 1 to 5, wherein the compound is of Formula I(a): O N R5 N R2 R8 R7 or a pharmaceutically acceptable salt f.
7. The compound of claim 6, wherein R6 is C1-C6 haloalkyl.
8. The nd of claim 7, wherein R6 is –CH2CF(CH3)2.
9. The compound of claim 6, wherein R7 is unsubstituted C1-C6 alkyl and R8 is hydrogen.
10. The compound of any one of claims 1 to 9, wherein the compound is of Formula I(c): N R5 N R2 R8 R7 or a pharmaceutically acceptable salt thereof.
11. The compound of claim 10, wherein R6 is C1-C6haloalkyl.
12. The compound of claim 11, wherein R6 is –CH2CF(CH3)2.
13. The compound of claim 12, wherein R7 is unsubstituted C1-C6 alkyl and R8 is en.
14. The compound of any one of claims 1 to 13, wherein the compound is selected from: O N O N H H N N N F N F , , or a pharmaceutically acceptable salt thereof.
15. The compound of claim 14, n the compound is: O N N F or a pharmaceutically acceptable salt thereof.
16. A composition comprising a nd according to claim 1 and a pharmaceutically acceptable r.
17. Use of a therapeutically effective amount of the compound of claim 1, optionally with a pharmaceutically acceptable carrier in the manufacture of a medicament for treating a disorder mediated by the estrogen receptor in a human patient.
18. The use of claim 17, wherein the disorder is selected from the group consisting of breast cancer, n cancer, endometrial cancer, l cancer, lung cancer, bone cancer, uterine cancer and endometriosis.
19. The use of claim 17 or claim 18, wherein the medicament further comprises another anticancer agent for the ent of cancer.
20. The use of any one of claims 17 to 19, wherein the medicament further comprises an estrogen or a partial estrogen receptor antagonist for the treatment of a nopausal disorder.
21. The compound of claim 14, wherein the compound is: O N N F or a pharmaceutically acceptable salt f.
22. The use of claim 18, wherein the disorder is breast cancer. Free drug concentration in BALB/c mice, 5mg/kg PO AUC24 35 I (hr-pg/ml) 30 -I-de B 405 dacre cpd 107 225 0 KKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKKK O 4 8 12 16 20 24 hours cccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccccc Free {img mnmntratian in BALM: make, Smgfkg PO 139 MCI?“ «News: 1895 149 *G‘na?acre cpd 1&2 5‘33 pIC50
Priority Applications (1)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| NZ779654A NZ779654A (en) | 2015-10-01 | 2016-09-29 | Tetrahydro-1h-pyrido[3,4-b]indole anti-estrogenic drugs |
Applications Claiming Priority (2)
| Application Number | Priority Date | Filing Date | Title |
|---|---|---|---|
| US201562235900P | 2015-10-01 | 2015-10-01 | |
| PCT/US2016/054549 WO2017059139A1 (en) | 2015-10-01 | 2016-09-29 | TETRAHYDRO-1H-PYRIDO[3,4-b]INDOLE ANTI-ESTROGENIC DRUGS |
Publications (2)
| Publication Number | Publication Date |
|---|---|
| NZ741130A true NZ741130A (en) | 2024-11-29 |
| NZ741130B2 NZ741130B2 (en) | 2025-03-04 |
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Legal Events
| Date | Code | Title | Description |
|---|---|---|---|
| PSEA | Patent sealed | ||
| RENW | Renewal (renewal fees accepted) |
Free format text: PATENT RENEWED FOR 1 YEAR UNTIL 29 SEP 2026 BY COMPUTER PACKAGES INC Effective date: 20250917 |